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Geographical variations in the incidence and prevalence of multiple sclerosis have been reported globally. Latitude as a surrogate for exposure to ultraviolet radiation but also other lifestyle and environmental factors are regarded as drivers of this variation. No previous studies evaluated geographical variation in the risk of secondary progressive multiple sclerosis, an advanced form of multiple sclerosis that is characterized by steady accrual of irreversible disability. We evaluated differences in the risk of secondary progressive multiple sclerosis in relation to latitude and country of residence, modified by high-to-moderate efficacy immunotherapy in a geographically diverse cohort of patients with relapsing-remitting multiple sclerosis. The study included relapsing-remitting multiple sclerosis patients from the global MSBase registry with at least one recorded assessment of disability. Secondary progressive multiple sclerosis was identified as per clinician diagnosis. Sensitivity analyses used the operationalized definition of secondary progressive multiple sclerosis and the Swedish decision tree algorithm. A proportional hazards model was used to estimate the cumulative risk of secondary progressive multiple sclerosis by country of residence (latitude), adjusted for sex, age at disease onset, time from onset to relapsing-remitting phase, disability (Multiple Sclerosis Severity Score) and relapse activity at study inclusion, national multiple sclerosis prevalence, government health expenditure, and proportion of time treated with high-to-moderate efficacy disease-modifying therapy. Geographical variation in time from relapsing-remitting phase to secondary progressive phase of multiple sclerosis was modelled through a proportional hazards model with spatially correlated frailties. We included 51 126 patients (72% female) from 27 countries. The median survival time from relapsing-remitting phase to secondary progressive multiple sclerosis among all patients wa

Background Adherence and persistence are critical to optimising therapeutic benefit from disease-modifying therapies (DMTs) in relapsing-remitting multiple sclerosis (RRMS). This prospective, open-label, multicentre, observational study (AubPRO), conducted in 13 hospital-based neurology clinics around Australia, describes treatment satisfaction in patients newly initiated on teriflunomide (Aubagio) and evaluates the use of an electronic patient-reported outcome (PRO) tool. Methods Patients (≥18 years) newly initiated on teriflunomide (14 mg/day) were followed up at 24 and 48 weeks. Patients completed questionnaires and pill counts electronically using MObile Data in Multiple Sclerosis. The primary endpoint was treatment satisfaction, measured by the Treatment Satisfaction Questionnaire for Medication (TSQM, V.1.4), at week 48. Secondary endpoints included treatment satisfaction at week 24, other PRO scales, clinical outcomes, medication adherence and safety. Results Patients (n=103; 54 (52.4%) treatment naive) were mostly female (n=82 (79.6%)), aged 49.5 (11.8) years, with MS duration since symptom onset of 9.1 (11.8) years and a median Expanded Disability Status Scale score of 1.0. Mean treatment satisfaction scores were high (≥60%) across all domains of the TSQM V.1.4 at week 24 and at week 48. Compared with week 24, week 48 treatment satisfaction increased for patients who were treatment naïve and for those previously on another oral or injectable DMT. Over 48 weeks, PROs remained stable across a range of measures including disability, physical health, emotional health and mobility, and there were improvements in work capacity and daily life activity. Adherence was high throughout the study with mean compliance (pill counts) of 93.2%±6.26%, and 98 of 103 (95.1%) patients remained relapse-free. Conclusion This cohort of Australian patients with RRMS, newly initiated on teriflunomide, and treated in a real-world clinical practice setting, reported high treatment sa

Background/objective: Observational clinical data from cladribine-treated patients with relapsing forms of multiple sclerosis (MS) were recorded in the Australian MS registry powered by the MSBase registry platform (5-year follow-up) and analysed to complement information from the pivotal cladribine clinical trials in MS. Method(s): A cohort of 90 cladribine-treated patients with follow-up data reported by treating physicians and recorded in the Australian MSBase registry (database lock February 2016) were examined. Clinical data included Expanded Disability Status Scale (EDSS) scores, relapses and other disease-modifying drugs (DMDs) administered before and after cladribine treatment. Result(s): Mean age on starting cladribine was 47 years; mean age at MS onset was 34 years, and median baseline EDSS score was 5.25. Disability trajectories in patients with sufficient follow-up suggested an overall increasing trend prior to cladribine treatment which was reduced during the 2-year post-treatment. Approximately 80% of patients were EDSS progression-free, 65% remained relapse-free after 2 years and median time to next DMD was 1.7 years. Conclusion(s): These observational data suggest a disease-modifying effect in this cohort of relapsing MS patients characterised by older and more disabled patients. Since these data represent a single-arm cohort, clinical trials and larger comparative post-marketing studies are needed to validate and extend these findings.Copyright © The Author(s), 2020.

BACKGROUND/OBJECTIVE: Observational clinical data from cladribine-treated patients with relapsing forms of multiple sclerosis (MS) were recorded in the Australian MS registry powered by the MSBase registry platform (5-year follow-up) and analysed to complement information from the pivotal cladribine clinical trials in MS. METHODS: A cohort of 90 cladribine-treated patients with follow-up data reported by treating physicians and recorded in the Australian MSBase registry (database lock February 2016) were examined. Clinical data included Expanded Disability Status Scale (EDSS) scores, relapses and other disease-modifying drugs (DMDs) administered before and after cladribine treatment. RESULTS: Mean age on starting cladribine was 47 years; mean age at MS onset was 34 years, and median baseline EDSS score was 5.25. Disability trajectories in patients with sufficient follow-up suggested an overall increasing trend prior to cladribine treatment which was reduced during the 2-year post-treatment. Approximately 80% of patients were EDSS progression-free, 65% remained relapse-free after 2 years and median time to next DMD was 1.7 years. CONCLUSION: These observational data suggest a disease-modifying effect in this cohort of relapsing MS patients characterised by older and more disabled patients. Since these data represent a single-arm cohort, clinical trials and larger comparative post-marketing studies are needed to validate and extend these findings.

Background: Cladribine has recently been introduced to the armamentarium of therapies for relapsing MS. Objective(s): To report relapses and disability in patients who were treated with cladribine as part of a product familiarisation program in Australia in 2011. Method(s): Patients exposed to oral cladribine, cumulative dose 1.75 mg/kg, between January and July 2011, enrolled in the MSBase registry were included. Incidence of relapses and disability (EDSS) were reported by the patients' treating physicians and recorded in the MSBase database. Result(s): This cohort of patients were older and had a higher EDSS at commencing oral cladribine than patients in the clinical trials of oral cladribine. Mean age at commencing cladribine was 47 years, age at MS onset was 34 years, duration of MS was 13 years and median EDSS score was 5.25. Disability trajectories suggested an overall increasing trend prior to treatment with cladribine, which was reduced during the 2 years following treatment. Based on EDSS scores, approximately 80% of patients were free from progression, 65% of patients remained relapse free after 2 years and median time to next DMT was 1.7 years. Conclusion(s): The data from the Australian oral cladribine product familiarisation program complement the information form clinical trials and a head-to-head comparison of observational data. This information suggests cladribine is associated with reduction in the rate of disability worsening for at least two years from the initial treatment administration. The studied data are limited and representative post-marketing studies, including safety surveillance, are needed.

Neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) show overlap in their clinical features. We performed an analysis of relapses with the aim of determining differences between the two conditions. Cases of NMOSD and age- and sex-matched MS controls were collected from across Australia and New Zealand. Demographic and clinical information, including relapse histories, were recorded using a standard questionnaire. There were 75 cases of NMOSD and 101 MS controls. There were 328 relapses in the NMOSD cases and 375 in MS controls. Spinal cord and optic neuritis attacks were the most common relapses in both NMOSD and MS. Optic neuritis (p < 0.001) and area postrema relapses (P = 0.002) were more common in NMOSD and other brainstem attacks were more common in MS (p < 0.001). Prior to age 30 years, attacks of optic neuritis were more common in NMOSD than transverse myelitis. After 30 this pattern was reversed. Relapses in NMOSD were more likely to be treated with acute immunotherapies and were less likely to recover completely. Analysis by month of relapse in NMOSD showed a trend toward reduced risk of relapse in February to April compared to a peak in November to January (P = 0.065). Optic neuritis and transverse myelitis are the most common types of relapse in NMOSD and MS. Optic neuritis tends to occur more frequently in NMOSD prior to the age of 30, with transverse myelitis being more common thereafter. Relapses in NMOSD were more severe. A seasonal bias for relapses in spring-summer may exist in NMOSD.

Over recent years, human autoantibodies targeting myelin oligodendrocyte glycoprotein (MOG Ab) have been associated with monophasic and relapsing central nervous system demyelination involving the optic nerves, spinal cord, and brain. While the clinical relevance of MOG Ab detection is becoming increasingly clear as therapeutic and prognostic differences from multiple sclerosis are acknowledged, an in-depth characterization of human MOG Ab is required to answer key challenges in patient diagnosis, treatment, and prognosis. Herein, we investigated the epitope, binding sensitivity, and affinity of MOG Ab in a cohort of 139 and 148 MOG antibody-seropositive children and adults (n = 287 patients at baseline, 130 longitudinal samples, and 22 cerebrospinal fluid samples). MOG extracellular domain was also immobilized to determine the affinity of MOG Ab. MOG Ab response was of immunoglobulin G1 isotype, and was of peripheral rather than intrathecal origin. High affinity MOG Ab were detected in 15% paediatric and 18% adult sera. More than 75% of paediatric and adult MOG Ab targeted a dominant extracellular antigenic region around Proline42. MOG Ab titers fluctuated over the progression of disease, but affinity and reactivity to Proline42 remained stable. Adults with a relapsing course intrinsically presented with a reduced immunoreactivity to Proline42 and had a more diverse MOG Ab response, a feature that may be harnessed for predicting relapse. Higher titers of MOG Ab were observed in more severe phenotypes and during active disease, supporting the pathogenic role of MOG Ab. Loss of MOG Ab seropositivity was observed upon conformational changes to MOG, and this greatly impacted the sensitivity of the detection of relapsing disorders, largely considered as more severe. Careful consideration of the binding characteristics of autoantigens should be taken into account when detecting disease-relevant autoantibodies.

• Multiple sclerosis (MS) is an autoimmune disease of the central nervous system with a multifactorial aetiology and highly variable natural history. • A growing understanding of the immunopathogenesis of the condition has led to an expanding array of therapies for this previously untreatable disease. • While a cure for MS remains elusive, the potential to reduce inflammatory disease activity by preventing relapses and minimising disease progression is achievable. • The importance of early treatment in minimising long-term disability is increasingly recognised. • Most of the newer, more effective therapies are associated with risks and practical problems that necessitate an active management strategy and continuous vigilance. • While the initiation of these therapies is likely to remain the responsibility of neurologists, other specialist physicians and general practitioners will be involved in the identification and management of adverse effects.